membranous nephropathy

Membranous GN

Primary (75%) & secondary. Commonest form in adults 33%. Secondary :

Collagen vascular disease SLE 10 – 20 % ,Rh.arthritis,dermatomyosiltis,

thyroid disease, ankylosing spondylitis,MCD etc……

Infection : HIV, HB, C & G,

syphilis,malaria,shistosomiasis.leprosy,filariasis etc….

Drugs like captopril , gold, penicillamine etc…

Chemicals like formaldehyde. Tumors of solid organs. Familial , MS & sarcoidosis. Graft versus host disease chronic type, De novo in allograft resulting in up to

50% loss of graft in 1.5 – 2 % Recurrence in graft 3-7% after

10/12,CRF in 4ys.

Immuonological disease with subepithelial AgAb complex deposition.

C5b-C9 is a diagnostic test for following activity.

Male : female 2:1 Peak incidence around 4th & 5th

decades. 60 – 70 % NS 20 – 30 % spontaneous remission. 20 – 30 % progress to CRF. 70 – 90 % 10 ys renal survival.

Membranous Nephropathy

Saw tooth appearance

Saw tooth appearance

The immune deposits in membranous glomerulonephritis are located on the subepithelial, or outer aspect of the glomerular basement membrane as illustrated

Silver stain

The capillary walls are thickened and subepithelial "spikes" are present, representing elaboration of basement membrane between subepithelial immune deposits.

Electron microscopy

numerous subepithelial electron dense deposits separated by basement membrane, correlating with the "spikes" seen by light microscopy .

EM

EM of Membranous GN

Non-proliferative GN with CW thickening. The deposition is shown to have spikes

with trichrome stains late in the disease. Patchy or diffuse fibrosis with severity &

time. Deposition in places other than Sub.End

favors secondary types. IgG, IgM, IgA & light chains ê&ë.

Stages Normal Light microscopy appearance . Electron microscopy shows few deposition with

no basement memb. projections.Numerous deposits with projections.New extracellular material surround the

deposits.Dense deposits become electron lucent & the

BM become thick.Subendothelial disturbance & normal

S.Epithelail.

Deposits

Deposits Membrane

Epithelia

l cell

Urinary space

DepositDeposit

Capillary Lumen

Natural History of Membranous GNMost remit

24 – 40 % CRF

complications

Hypovolaemia with diuretics. Thrombosis . HTN . Hyperlipidaemia . Fluids overload. Serositis . IHD Infections .

SLE Differentiation between membranous nephropathy in SLE and the idiopathic type

Treatment Imuonsupression in MGN. Identify 2dry causes. Rate of progression : Low risk : 5%

proteinuria < 4 gm/day maintained for 6/12 Medium risk :

4 – 8 gm/day 6/12 steroid alone in not effective High risk :

abnormal renal function +/- proteinuria 6/12.

Treatment strategies

Specific immuonosupression Non-specific for proteinuria Treatment of secondary effects Prophylaxis

Specific therapy:

Corticosteroids:

Are not effective on their own especially for long term benefits.

Chlorambucil Ponticelli`s regimen :

steroids as pulse therapy initially 1 gm methylprednisolone IV for 3 days

0.5mg/kg/day chlorambucil for 1/12 alternating with

0.5 mg/kg/day prenisolone for 1/12

The two month cycle is repeated three times. At 10 ys 8 % Vs 40 % lost their RF.

Cyclophosphamide Different results in different studies.Falk & his group used pulsed Cyc with

pred for 2 ys showed no difference Non-randomized study showed the

reverse .

Cyclosporine

Improve proteinuria & preserve renal function in up to 2/3 of patients.

Some showed slow response of almost one year to a achieve remission .

Cattran et al showed that Cyc slowed progression of RF

May be the data is better in high risk groups with cyc than with other cytotoxic drugs.

Dose :3.5 – 4 mg/kg trough level of 150 – 200

The dose can be increased if no appropriate response.

Cell cept Weak data are available but showed

benefits in the form of protein excretion .

IV ImmuonoglobulinsBinds to complement hence decreasing

their activity .Dose :

0.4gm/day for three daysFollowed by :

0.4gm/day for 3 days at 3/52 intervalFollowed by :

0.4gm/day for 1day at 3/52 interval for 6 – 9/12

Azathioprine

Recommendations is that it is of no benefits awaiting large randomized trials.

NSAID

Can rarely cause MGN & lead to deterioration of the renal function.

Others

Rituximab Pentoxiphylline Tacrolimus

Nonspecific treatment

BP control ( ACEI ,ACERB, Non-dihydropyrdine )

Protein restriction 0.7 – 0.8 gm/kg + 1 gm for each gm loss of protein in urine.

Lipid control Diuretics Salt & water restriction Anticoagulation

Prophylaxis Guard against pneuomocystis cariniiBiphosphonates especially in

postmenopausal women .

Recommendations

Asymptomatic patients with non-nephrotic range proteinuria should be given general treatment & followed up.

Asymptomatic patients with nephrotic range proteinuria with controllable oedema should be observed for prolonged period since 65% have spontaneous remission.

Active therapy is indicated in those who are likely to progress :

- High S.Cr - Marked oedema - Proteinuria > 10gm/day- Evidence of scarring - Tubulointerstitial affection >10%- Thromboembolic disease